PROJECT SUMMARY Drinking and smoking are closely related. Adults with DSM-5 current alcohol use disorder (AUD) who smoke cigarettes are at significantly elevated risk for adverse health outcomes and smoking cessation failure. Reduction in cigarette nicotine content has been proposed as a strategy to promote smoking cessation and improve public health, yet studies have not yet evaluated how adults with AUD who smoke respond to reduced nicotine cigarettes (RNCs). Such studies can also test behavioral mechanisms underlying the close association between drinking and smoking, providing information for future integrated interventions that aim to reduce both drinking and smoking. The current proposal examines response to two RNCs, one with low nicotine content (RNC Low; 0.12mg) and one with moderate nicotine content (RNC Moderate; 0.8mg) in daily smokers with and without AUD. Participants (N = 70) will attend a total of five visits to the laboratory. The first visit will be to classify participants as either AUD (n = 35) or Non AUD (n = 35) and gather baseline data. Participants will be assigned to undergo two experimental conditions (i.e., exclusive smoking of RNC Low or Moderate in their home environment for 7 days) in a double-blind, randomized, crossover design. The two experimental conditions will be separated by a 7-day period of return to smoking of participants? own brand of cigarette. On the first and last day of each of the two experimental conditions, participants will smoke the assigned RNC in the laboratory, and data on toxicant exposure (i.e., boost in exhaled carbon monoxide and plasma nicotine and cotinine; solanesol from smoked cigarette butts), subjective acceptability (i.e., subjective response; risk perceptions; relative reinforcing efficacy); and smoking compensation (i.e., smoking topography measures) related to the smoked RNC will be collected. During each 7-day period of exposure to the RNCs, participants will provide daily data on alcohol and nicotine use, nicotine withdrawal, smoking urge, and alcohol urge via telephone-based Interactive Voice Response technology. The strength of our study design is that we can evaluate both between-group (i.e., AUD vs. Non AUD) and within-person (i.e., RNC Low vs. Moderate) differences in response to RNCs and, furthermore, can examine whether increased nicotine withdrawal, smoking urge, and alcohol urge mediate the relation between decreased nicotine exposure and alcohol consumption. Results from this study will show what mechanisms underlying drinking and smoking may need to be addressed in future integrated interventions for both problems and will immediately inform the practical implementation of market-wide reductions in cigarette nicotine content among smokers with AUD.